Exploring the Pangenome and Immuno-Proteome of Urinary Tract Infection Causing Bacterial Pathogens to Unravel Vaccine Targets

Abstract

Urinary tract infections are a growing concern for the society in terms of morbidity and health care economic burden worldwide, emphasizing the prerequisite for new vaccine interventions in the current scenario of antibiotic resistance. The current study aims at prioritizing broad-spectrum vaccine targets, present in different uropathogens, through a pan-genomics strategy coupled with a comparative genomics and immuno-proteomics analysis. The inter-specie pan-genome analysis was not fruitful in obtaining any conserved genome, therefore intra-specie pan-genome analysis was performed which revealed 13556, 9266, 10713, 291789, 4031, 4285, 4195 and 3924 genes for E. coloi, K. pneumoniae, K. oxytoca, P.aeruginosa, E. faecalis, E. faecium, S. aureus and P. mirabilis respectively. The core genomesubsets estimated to carry 2595, 4132, 3534, 4151, 2169, 1909, 1902 and 2969 for E. coloi, K. pneumoniae, K. oxytoca, P.aeruginosa, E. faecalis, E. faecium, S. aureus and P. mirabilis respectively. Moreover the pan-genome of these pathogens was also analyzed for the presence of resistance genes and 564 resistance genes were identified. The discrete core-genomes of all the pathogens under analysis were identified and considered for filtration through five different parameters such as host non homology analysis (2,1169), essentiality analysis (5,824), virulence factor analysis (3,747), <2 helices analysis (15,033) and sub-cellular localization (1488). The analyses revealed a set of promising vaccine targets present in the core-genome of individual uropathogenic species. The novel vaccine targets namely, Omp N, toluene efflux pump outer membrane precursor, zinc binding, phosphor ethyl pyramidine kinase, 50S ribosomal L13, Fe binding precursor, N-acetylneuraminic acid outer membrane channel and family RND efflux system outer membrane lipo, were found to be functionally important with at least >5 metabolic interactors, also found to be present in a wide range of other urogenital disease causing bacteria and having <110kDa molecular viii weight, makes them ideal vaccine candidates. Immuno proteomic analysis further illustrated the ability of these vaccine targets to trigger both B-cell and T-cell activation. The identified vaccine targets may assist in designing and development of broad-spectrum vaccines against these uropathogens. The pipeline can also be utilized to identify vaccine trgets against other pathogens.